Multimodal speech biomarkers for remote monitoring of ALS disease progression.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that severely impacts affected persons' speech and motor functions, yet early detection and tracking of disease progression remain challenging. The current gold standard for monitoring ALS progression, the ALS functional rating scale - revised (ALSFRS-R), is based on subjective ratings of symptom severity, and may not capture subtle but clinically meaningful changes due to a lack of granularity. Multimodal speech measures which can be automatically collected from patients in a remote fashion allow us to bridge this gap because they are continuous-valued and therefore, potentially more granular at capturing disease progression. Here we investigate the responsiveness and sensitivity of multimodal speech measures in persons with ALS (pALS) collected via a remote patient monitoring platform in an effort to quantify how long it takes to detect a clinically-meaningful change associated with disease progression. We recorded audio and video from 278 participants and automatically extracted multimodal speech biomarkers (acoustic, orofacial, linguistic) from the data. We find that the timing alignment of pALS speech relative to a canonical elicitation of the same prompt and the number of words used to describe a picture are the most responsive measures at detecting such change in both pALS with bulbar (n = 36) and non-bulbar onset (n = 107). Interestingly, the responsiveness of these measures is stable even at small sample sizes. We further found that certain speech measures are sensitive enough to track bulbar decline even when there is no patient-reported clinical change, i.e. the ALSFRS-R speech score remains unchanged at 3 out of a total possible score of 4. The findings of this study have the potential to facilitate improved, accelerated and cost-effective clinical trials and care.

Predicting the severity of mood and neuropsychiatric symptoms from digital biomarkers using wearable physiological data and deep learning.

Neuropsychiatric symptoms (NPS) and mood disorders are common in individuals with mild cognitive impairment (MCI) and increase the risk of progression to dementia. Wearable devices collecting physiological and behavioral data can help in remote, passive, and continuous monitoring of moods and NPS, overcoming limitations and inconveniences of current assessment methods. In this longitudinal study, we examined the predictive ability of digital biomarkers based on sensor data from a wrist-worn wearable to determine the severity of NPS and mood disorders on a daily basis in older adults with predominant MCI. In addition to conventional physiological biomarkers, such as heart rate variability and skin conductance levels, we leveraged deep-learning features derived from physiological data using a self-supervised convolutional autoencoder. Models combining common digital biomarkers and deep features predicted depression severity scores with a correlation of r = 0.73 on average, total severity of mood disorder symptoms with r = 0.67, and mild behavioral impairment scores with r = 0.69 in the study population. Our findings demonstrated the potential of physiological biomarkers collected from wearables and deep learning methods to be used for the continuous and unobtrusive assessments of mental health symptoms in older adults, including those with MCI. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT05059353) on September 28, 2021, titled "Effectiveness and Safety of a Digitally Based Multidomain Intervention for Mild Cognitive Impairment".

Screening for RV Dysfunction Using Smartphone ECG Analysis App: Validation Study with Acute Pulmonary Embolism Patients.

Background: Acute pulmonary embolism (PE) is a critical condition where the timely and accurate assessment of right ventricular (RV) dysfunction is important for patient management. Given the limited availability of echocardiography in emergency departments (EDs), an artificial intelligence (AI) application that can identify RV dysfunction from electrocardiograms (ECGs) could improve the treatment of acute PE. Methods: This retrospective study analyzed adult acute PE patients in an ED from January 2021 to December 2023. We evaluated a smartphone application which analyzes printed ECGs to generate digital biomarkers for various conditions, including RV dysfunction (QCG-RVDys). The biomarker's performance was compared with that of cardiologists and emergency physicians. Results: Among 116 included patients, 35 (30.2%) were diagnosed with RV dysfunction. The QCG-RVDys score demonstrated significant effectiveness in identifying RV dysfunction, with a receiver operating characteristic-area under the curve (AUC) of 0.895 (95% CI, 0.829-0.960), surpassing traditional biomarkers such as Troponin I (AUC: 0.692, 95% CI: 0.536-0.847) and ProBNP (AUC: 0.655, 95% CI: 0.532-0.778). Binarized based on the Youden Index, QCG-RVDys achieved an AUC of 0.845 (95% CI: 0.778-0.911), with a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 91.2% (95% CI: 82.4-100%), 77.8% (95% CI: 69.1-86.4%), 63.3% (95% CI: 54.4-73.9%), and 95.5% (95% CI: 90.8-100%), respectively, significantly outperforming all the expert clinicians, with their AUCs ranging from 0.628 to 0.683. Conclusions: The application demonstrates promise in rapidly assessing RV dysfunction in acute PE patients. Its high NPV could streamline patient management, potentially reducing the reliance on echocardiography in emergency settings.

An automatic measure for speech intelligibility in dysarthrias-validation across multiple languages and neurological disorders.

Introduction: Dysarthria, a motor speech disorder caused by muscle weakness or paralysis, severely impacts speech intelligibility and quality of life. The condition is prevalent in motor speech disorders such as Parkinson's disease (PD), atypical parkinsonism such as progressive supranuclear palsy (PSP), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Improving intelligibility is not only an outcome that matters to patients but can also play a critical role as an endpoint in clinical research and drug development. This study validates a digital measure for speech intelligibility, the ki: SB-M intelligibility score, across various motor speech disorders and languages following the Digital Medicine Society (DiMe) V3 framework. Methods: The study used four datasets: healthy controls (HCs) and patients with PD, HD, PSP, and ALS from Czech, Colombian, and German populations. Participants' speech intelligibility was assessed using the ki: SB-M intelligibility score, which is derived from automatic speech recognition (ASR) systems. Verification with inter-ASR reliability and temporal consistency, analytical validation with correlations to gold standard clinical dysarthria scores in each disease, and clinical validation with group comparisons between HCs and patients were performed. Results: Verification showed good to excellent inter-rater reliability between ASR systems and fair to good consistency. Analytical validation revealed significant correlations between the SB-M intelligibility score and established clinical measures for speech impairments across all patient groups and languages. Clinical validation demonstrated significant differences in intelligibility scores between pathological groups and healthy controls, indicating the measure's discriminative capability. Discussion: The ki: SB-M intelligibility score is a reliable, valid, and clinically relevant tool for assessing speech intelligibility in motor speech disorders. It holds promise for improving clinical trials through automated, objective, and scalable assessments. Future studies should explore its utility in monitoring disease progression and therapeutic efficacy as well as add data from further dysarthrias to the validation.

Artificial Intelligence-Based Digital Biomarkers for Type 2 Diabetes: A Review.

Type 2 diabetes mellitus (T2DM), a complex metabolic disorder that burdens the healthcare system, requires early detection and treatment. Recent strides in digital health technologies coupled with artificial intelligence (AI) may have the potential to revolutionize T2DM screening, diagnosis of complications, and management through the development of digital biomarkers. This review provides an overview of the potential applications of AI-driven biomarkers in the context of screening, diagnosing complications, and managing patients with T2DM. The benefits of using multi-sensor devices to develop digital biomarkers are discussed. The summary of these findings and patterns between model architecture and sensor type are presented. Additionally, we highlight the pivotal role of AI techniques in clinical intervention and implementation, encompassing clinical decision support systems, telemedicine interventions, and population health initiatives. Challenges such as data privacy, algorithm interpretability, and regulatory considerations are also highlighted, alongside future research directions to explore the use of AI-driven digital biomarkers in T2DM screening and management.

Unraveling the physiological and psychosocial signatures of pain by machine learning.

BACKGROUND: Pain is a complex subjective experience, strongly impacting health and quality of life. Despite many attempts to find effective solutions, present treatments are generic, often unsuccessful, and present significant side effects. Designing individualized therapies requires understanding of multidimensional pain experience, considering physical and emotional aspects. Current clinical pain assessments, relying on subjective one-dimensional numeric self-reports, fail to capture this complexity. METHODS: To this aim, we exploited machine learning to disentangle physiological and psychosocial components shaping the pain experience. Clinical, psychosocial, and physiological data were collected from 118 chronic pain and healthy participants undergoing 40 pain trials (4,697 trials). FINDINGS: To understand the objective response to nociception, we classified pain from the physiological signals (accuracy >0.87), extracting the most important biomarkers. Then, using multilevel mixed-effects models, we predicted the reported pain, quantifying the mismatch between subjective level and measured physiological response. From these models, we introduced two metrics: TIP (subjective index of pain) and Φ (physiological index). These represent possible added value in the clinical process, capturing psychosocial and physiological pain dimensions, respectively. Patients with high TIP are characterized by frequent sick leave from work and increased clinical depression and anxiety, factors associated with long-term disability and poor recovery, and are indicated for alternative treatments, such as psychological ones. By contrast, patients with high Φ show strong nociceptive pain components and could benefit more from pharmacotherapy. CONCLUSIONS: TIP and Φ, explaining the multidimensionality of pain, might provide a new tool potentially leading to targeted treatments, thereby reducing the costs of inefficient generic therapies. FUNDING: RESC-PainSense, SNSF-MOVE-IT197271.

Identifying digital biomarkers of illness activity and treatment response in bipolar disorder with a novel wearable device (TIMEBASE): protocol for a pragmatic observational clinical study.

BACKGROUND: Bipolar disorder is highly prevalent and consists of biphasic recurrent mood episodes of mania and depression, which translate into altered mood, sleep and activity alongside their physiological expressions. AIMS: The IdenTifying dIgital bioMarkers of illnEss activity and treatment response in BipolAr diSordEr with a novel wearable device (TIMEBASE) project aims to identify digital biomarkers of illness activity and treatment response in bipolar disorder. METHOD: We designed a longitudinal observational study including 84 individuals. Group A comprises people with acute episode of mania (n = 12), depression (n = 12 with bipolar disorder and n = 12 with major depressive disorder (MDD)) and bipolar disorder with mixed features (n = 12). Physiological data will be recorded during 48 h with a research-grade wearable (Empatica E4) across four consecutive time points (acute, response, remission and episode recovery). Group B comprises 12 people with euthymic bipolar disorder and 12 with MDD, and group C comprises 12 healthy controls who will be recorded cross-sectionally. Psychopathological symptoms, disease severity, functioning and physical activity will be assessed with standardised psychometric scales. Physiological data will include acceleration, temperature, blood volume pulse, heart rate and electrodermal activity. Machine learning models will be developed to link physiological data to illness activity and treatment response. Generalisation performance will be tested in data from unseen patients. RESULTS: Recruitment is ongoing. CONCLUSIONS: This project should contribute to understanding the pathophysiology of affective disorders. The potential digital biomarkers of illness activity and treatment response in bipolar disorder could be implemented in a real-world clinical setting for clinical monitoring and identification of prodromal symptoms. This would allow early intervention and prevention of affective relapses, as well as personalisation of treatment.

Multimodal Speech Biomarkers for Remote Monitoring of ALS Disease Progression.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that severely impacts affected persons' speech and motor functions, yet early detection and tracking of disease progression remain challenging. The current gold standard for monitoring ALS progression, the ALS functional rating scale - revised (ALSFRS-R), is based on subjective ratings of symptom severity, and may not capture subtle but clinically meaningful changes due to a lack of granularity. Multimodal speech measures which can be automatically collected from patients in a remote fashion allow us to bridge this gap because they are continuous-valued and therefore, potentially more granular at capturing disease progression. Here we investigate the responsiveness and sensitivity of multimodal speech measures in persons with ALS (pALS) collected via a remote patient monitoring platform in an effort to quantify how long it takes to detect a clinically-meaningful change associated with disease progression. We recorded audio and video from 278 participants and automatically extracted multimodal speech biomarkers (acoustic, orofacial, linguistic) from the data. We find that the timing alignment of pALS speech relative to a canonical elicitation of the same prompt and the number of words used to describe a picture are the most responsive measures at detecting such change in both pALS with bulbar (n = 36) and non-bulbar onset (n = 107). Interestingly, the responsiveness of these measures is stable even at small sample sizes. We further found that certain speech measures are sensitive enough to track bulbar decline even when there is no patient-reported clinical change, i.e. the ALSFRS-R speech score remains unchanged at 3 out of a total possible score of 4. The findings of this study have the potential to facilitate improved, accelerated and cost-effective clinical trials and care.

Overarm Training Tolerance: A Pilot Study on the Use of Muscle Oxygen Saturation as a Biomarker.

Ulnar collateral ligament (UCL) tears occur due to the prolonged exposure and overworking of joint stresses, resulting in decreased strength in the flexion and extension of the elbow. Current rehabilitation approaches for UCL tears involve subjective assessments (pain scales) and objective measures such as monitoring joint angles and range of motion. The main goal of this study is to find out if using wearable near-infrared spectroscopy technology can help measure digital biomarkers like muscle oxygen levels and heart rate. These measurements could then be applied to athletes who have been injured. Specifically, measuring muscle oxygen levels will help us understand how well the muscles are using oxygen. This can indicate improvements in how the muscles are healing and growing new blood vessels after reconstructive surgery. Previous research studies demonstrated that there remains an unmet clinical need to measure biomarkers to provide continuous, internal data on muscle physiology during the rehabilitation process. This study's findings can benefit team physicians, sports scientists, athletic trainers, and athletes in the identification of biomarkers to assist in clinical decisions for optimizing training regimens for athletes that perform overarm movements; the research suggests pathways for possible earlier detection, and thus earlier intervention for injury prevention.

Advancements in eye movement measurement technologies for assessing neurodegenerative diseases.

Eye movements have long been recognized as a valuable indicator of neurological conditions, given the intricate involvement of multiple neurological pathways in vision-related processes, including motor and cognitive functions, manifesting in rapid response times. Eye movement abnormalities can indicate neurological condition severity and, in some cases, distinguish between disease phenotypes. With recent strides in imaging sensors and computational power, particularly in machine learning and artificial intelligence, there has been a notable surge in the development of technologies facilitating the extraction and analysis of eye movements to assess neurodegenerative diseases. This mini-review provides an overview of these advancements, emphasizing their potential in offering patient-friendly oculometric measures to aid in assessing patient conditions and progress. By summarizing recent technological innovations and their application in assessing neurodegenerative diseases over the past decades, this review also delves into current trends and future directions in this expanding field.

A novel digital tool for detection and monitoring of amyotrophic lateral sclerosis motor impairment and progression via keystroke dynamics.

Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative condition leading to progressive muscle weakness, atrophy, and ultimately death. Traditional ALS clinical evaluations often depend on subjective metrics, making accurate disease detection and monitoring disease trajectory challenging. To address these limitations, we developed the nQiALS toolkit, a machine learning-powered system that leverages smartphone typing dynamics to detect and track motor impairment in people with ALS. The study included 63 ALS patients and 30 age- and sex-matched healthy controls. We introduce the three core components of this toolkit: the nQiALS-Detection, which differentiated ALS from healthy typing patterns with an AUC of 0.89; the nQiALS-Progression, which separated slow and fast progression at specific thresholds with AUCs ranging between 0.65 and 0.8; and the nQiALS-Fine Motor, which identified subtle progression in fine motor dysfunction, suggesting earlier prediction than the state-of-the-art assessment. Together, these tools represent an innovative approach to ALS assessment, offering a complementary, objective metric to traditional clinical methods and which may reshape our understanding and monitoring of ALS progression.

DISPEL: A Python Framework for Developing Measures From Digital Health Technologies.

Goal: This paper introduces DISPEL, a Python framework to facilitate development of sensor-derived measures (SDMs) from data collected with digital health technologies in the context of therapeutic development for neurodegenerative diseases. Methods: Modularity, integrability and flexibility were achieved adopting an object-oriented architecture for data modelling and SDM extraction, which also allowed standardizing SDM generation, naming, storage, and documentation. Additionally, a functionality was designed to implement systematic flagging of missing data and unexpected user behaviors, both frequent in unsupervised monitoring. Results: DISPEL is available under MIT license. It already supports formats from different data providers and allows traceable end-to-end processing from raw data collected with wearables and smartphones to structured SDM datasets. Novel and literature-based signal processing approaches currently allow to extract SDMs from 16 structured tests (including six questionnaires), assessing overall disability and quality of life, and measuring performance outcomes of cognition, manual dexterity, and mobility. Conclusion: DISPEL supports SDM development for clinical trials by providing a production-grade Python framework and a large set of already implemented SDMs. While the framework has already been refined based on clinical trials' data, ad-hoc validation of the provided algorithms in their specific context of use is recommended to the users.

Transforming Cardiovascular Care With Artificial Intelligence: From Discovery to Practice: JACC State-of-the-Art Review.

Artificial intelligence (AI) has the potential to transform every facet of cardiovascular practice and research. The exponential rise in technology powered by AI is defining new frontiers in cardiovascular care, with innovations that span novel diagnostic modalities, new digital native biomarkers of disease, and high-performing tools evaluating care quality and prognosticating clinical outcomes. These digital innovations promise expanded access to cardiovascular screening and monitoring, especially among those without access to high-quality, specialized care historically. Moreover, AI is propelling biological and clinical discoveries that will make future cardiovascular care more personalized, precise, and effective. The review brings together these diverse AI innovations, highlighting developments in multimodal cardiovascular AI across clinical practice and biomedical discovery, and envisioning this new future backed by contemporary science and emerging discoveries. Finally, we define the critical path and the safeguards essential to realizing this AI-enabled future that helps achieve optimal cardiovascular health and outcomes for all.

Digital biomarkers: 3PM approach revolutionizing chronic disease management - EPMA 2024 position.

Non-communicable chronic diseases (NCDs) have become a major global health concern. They constitute the leading cause of disabilities, increased morbidity, mortality, and socio-economic disasters worldwide. Medical condition-specific digital biomarker (DB) panels have emerged as valuable tools to manage NCDs. DBs refer to the measurable and quantifiable physiological, behavioral, and environmental parameters collected for an individual through innovative digital health technologies, including wearables, smart devices, and medical sensors. By leveraging digital technologies, healthcare providers can gather real-time data and insights, enabling them to deliver more proactive and tailored interventions to individuals at risk and patients diagnosed with NCDs. Continuous monitoring of relevant health parameters through wearable devices or smartphone applications allows patients and clinicians to track the progression of NCDs in real time. With the introduction of digital biomarker monitoring (DBM), a new quality of primary and secondary healthcare is being offered with promising opportunities for health risk assessment and protection against health-to-disease transitions in vulnerable sub-populations. DBM enables healthcare providers to take the most cost-effective targeted preventive measures, to detect disease developments early, and to introduce personalized interventions. Consequently, they benefit the quality of life (QoL) of affected individuals, healthcare economy, and society at large. DBM is instrumental for the paradigm shift from reactive medical services to 3PM approach promoted by the European Association for Predictive, Preventive, and Personalized Medicine (EPMA) involving 3PM experts from 55 countries worldwide. This position manuscript consolidates multi-professional expertise in the area, demonstrating clinically relevant examples and providing the roadmap for implementing 3PM concepts facilitated through DBs.

Characterizing Longitudinal Patterns in Cognition, Mood, And Activity in Depression With 6-Week High-Frequency Wearable Assessment: Observational Study.

BACKGROUND: Cognitive symptoms are an underrecognized aspect of depression that are often untreated. High-frequency cognitive assessment holds promise for improving disease and treatment monitoring. Although we have previously found it feasible to remotely assess cognition and mood in this capacity, further work is needed to ascertain the optimal methodology to implement and synthesize these techniques. OBJECTIVE: The objective of this study was to examine (1) longitudinal changes in mood, cognition, activity levels, and heart rate over 6 weeks; (2) diurnal and weekday-related changes; and (3) co-occurrence of fluctuations between mood, cognitive function, and activity. METHODS: A total of 30 adults with current mild-moderate depression stabilized on antidepressant monotherapy responded to testing delivered through an Apple Watch (Apple Inc) for 6 weeks. Outcome measures included cognitive function, assessed with 3 brief n-back tasks daily; self-reported depressed mood, assessed once daily; daily total step count; and average heart rate. Change over a 6-week duration, diurnal and day-of-week variations, and covariation between outcome measures were examined using nonlinear and multilevel models. RESULTS: Participants showed initial improvement in the Cognition Kit N-Back performance, followed by a learning plateau. Performance reached 90% of individual learning levels on average 10 days after study onset. N-back performance was typically better earlier and later in the day, and step counts were lower at the beginning and end of each week. Higher step counts overall were associated with faster n-back learning, and an increased daily step count was associated with better mood on the same (P<.001) and following day (P=.02). Daily n-back performance covaried with self-reported mood after participants reached their learning plateau (P=.01). CONCLUSIONS: The current results support the feasibility and sensitivity of high-frequency cognitive assessments for disease and treatment monitoring in patients with depression. Methods to model the individual plateau in task learning can be used as a sensitive approach to better characterize changes in behavior and improve the clinical relevance of cognitive data. Wearable technology allows assessment of activity levels, which may influence both cognition and mood.

Digitally-enabled, person-centred care (PCC) in allergen immunotherapy: An ARIA-EAACI Position Paper.

In rhinitis and asthma, several mHealth apps have been developed but only a few have been validated. However, these apps have a high potential for improving person-centred care (PCC), especially in allergen immunotherapy (AIT). They can provide support in AIT initiation by selecting the appropriate patient and allergen shared decision-making. They can also help in (i) the evaluation of (early) efficacy, (ii) early and late stopping rules and (iii) the evaluation of (carried-over) efficacy after cessation of the treatment course. Future perspectives have been formulated in the first report of a joint task force (TF)-Allergic Rhinitis and Its Impact on Asthma (ARIA) and the European Academy of Allergy and Clinical Immunology (EAACI)-on digital biomarkers. The TF on AIT now aims to (i) outline the potential of the clinical applications of mHealth solutions, (ii) express their current limitations, (iii) make proposals regarding further developments for both clinical practice and scientific purpose and (iv) suggest which of the tools might best comply with the purpose of digitally-enabled PCC in AIT.

Innova4Health: an integrated approach for prevention of recurrence and personalized treatment of Major Depressive Disorder.

Background: Major Depressive Disorder (MDD) is a prevalent mental health condition characterized by persistent low mood, cognitive and physical symptoms, anhedonia (loss of interest in activities), and suicidal ideation. The World Health Organization (WHO) predicts depression will become the leading cause of disability by 2030. While biological markers remain essential for understanding MDD's pathophysiology, recent advancements in social signal processing and environmental monitoring hold promise. Wearable technologies, including smartwatches and air purifiers with environmental sensors, can generate valuable digital biomarkers for depression assessment in real-world settings. Integrating these with existing physical, psychopathological, and other indices (autoimmune, inflammatory, neuroradiological) has the potential to improve MDD recurrence prevention strategies. Methods: This prospective, randomized, interventional, and non-pharmacological integrated study aims to evaluate digital and environmental biomarkers in adolescents and young adults diagnosed with MDD who are currently taking medication. The study implements a sensor-integrated platform built around an open-source "Pothos" air purifier system. This platform is designed for scalability and integration with third-party devices. It accomplishes this through software interfaces, a dedicated app, sensor signal pre-processing, and an embedded deep learning AI system. The study will enroll two experimental groups (10 adolescents and 30 young adults each). Within each group, participants will be randomly allocated to Group A or Group B. Only Group B will receive the technological equipment (Pothos system and smartwatch) for collecting digital biomarkers. Blood and saliva samples will be collected at baseline (T0) and endpoint (T1) to assess inflammatory markers and cortisol levels. Results: Following initial age-based stratification, the sample will undergo detailed classification at the 6-month follow-up based on remission status. Digital and environmental biomarker data will be analyzed to explore intricate relationships between these markers, depression symptoms, disease progression, and early signs of illness. Conclusion: This study seeks to validate an AI tool for enhancing early MDD clinical management, implement an AI solution for continuous data processing, and establish an AI infrastructure for managing healthcare Big Data. Integrating innovative psychophysical assessment tools into clinical practice holds significant promise for improving diagnostic accuracy and developing more specific digital devices for comprehensive mental health evaluation.

Feasibility of Deploying Home-Based Digital Technology, Environmental Sensors, and Web-Based Surveys for Assessing Behavioral Symptoms and Identifying Their Precipitants in Older Adults: Longitudinal, Observational Study.

BACKGROUND: Apathy, depression, and anxiety are prevalent neuropsychiatric symptoms experienced by older adults. Early detection, prevention, and intervention may improve outcomes. OBJECTIVE: We aim to demonstrate the feasibility of deploying web-based weekly questionnaires inquiring about the behavioral symptoms of older adults with normal cognition, mild cognitive impairment, or early-stage dementia and to demonstrate the feasibility of deploying an in-home technology platform for measuring participant behaviors and their environment. METHODS: The target population of this study is older adults with normal cognition, mild cognitive impairment, or early-stage dementia. This is an observational, longitudinal study with a study period of up to 9 months. The severity of participant behavioral symptoms (apathy, depression, and anxiety) was self-reported weekly through web-based surveys. Participants' digital biomarkers were continuously collected at their personal residences and through wearables throughout the duration of the study. The indoor physical environment at each residence, such as light level, noise level, temperature, humidity, or air quality, was also measured using indoor environmental sensors. Feasibility was examined, and preliminary correlation analysis between the level of symptoms and the digital biomarkers and between the level of symptoms and the indoor environment was performed. RESULTS: At 13 months after recruitment began, a total of 9 participants had enrolled into this study. The participants showed high adherence rates in completing the weekly questionnaires (response rate: 275/278, 98.9%), and data collection using the digital technology appeared feasible and acceptable to the participants with few exceptions. Participants' severity of behavioral symptoms fluctuated from week to week. Preliminary results show that the duration of sleep onset and noise level are positively correlated with the anxiety level in a subset of our participants. CONCLUSIONS: This study is a step toward more frequent assessment of older adults' behavioral symptoms and holistic in situ monitoring of older adults' behaviors and their living environment. The goal of this study is to facilitate the development of objective digital biomarkers of neuropsychiatric symptoms and to identify in-home environmental factors that contribute to these symptoms.